Acalabrutinib is a Bruton tyrosine kinase inhibitor (BTKi) approved for use in the treatment of chronic lymphocytic leukemia (CLL). Herein, we present a patient successfully treated with reduced-dose acalabrutinib for CLL, with pre-existing hypogammaglobulinemia-type immunoglobulin G (IgG) and immunoglobulin M (IgM). The gene discussed is BTK; the disease is B-cell chronic lymphocytic leukemia.